Pharmacokinetic analysis of a combined chemoendocrine treatment with paclitaxel and toremifene for metastatic breast cancer.
BACKGROUND
Multidrug resistance protein could be a target for improving the efficacy of paclitaxel (PXL). Toremifene (TOR) may moderate P-gp-related drug resistance in vitro. Some P-gp moderators may change the pharmacokinetic parameters of PXL in vivo. A pharmacokinetic (PK) study in metastatic breast cancer patients (MBC) was conducted to determine the safety and efficacy of PXL and TOR.


METHODS
Fifteen patients received 80 mg/m(2) PXL (i.v.) weekly and 120 mg/body TOR (p.o.) daily. For the pharmacokinetic study, PXL was administered on days 1, 8, 15, 32, and 39; TOR was given from day 18 to the end of study. On days 1, 8, 15, 18, 32, and 39, blood samples were collected from the patients who received either PXL alone or PXL + TOR, and these were analyzed by high-performance liquid chromatography.


RESULTS
Among the 15 patients enrolled in the study, one showed a partial response, and eight had a stable disease. TOR caused no specific adverse events that were greater than grade 3, and its toxicity profile in combination with PXL was similar to that of PXL monotherapy. The PK profile of PXL was similar with or without TOR. The PK parameters of PXL indicated no inter- or intra-patient variability in previously treated patients with MBC. No increased PXL toxicity was observed.


CONCLUSIONS
The PK profile of combined PXL and TOR was similar to that of PXL monotherapy. The addition of TOR to PXL in previously treated patients with MBC appears safe.
Saeki
Toshiaki
T
Department of Breast Oncology, Saitama International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, 350-1298, Japan. tsaeki@saitama-med.ac.jp
Okita
Atsushi
A
Aogi
Kenjiro
K
Kakishita
Tomokazu
T
Okita
Riki
R
Taira
Naruto
N
Ohama
Yumi
Y
Takashima
Shigemitsu
S
Nishikawa
Kiyohiro
K
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D015996:Survival Rate; D014018:Tissue Distribution; D017312:Toremifene / Q000008:administration & dosage; D016896:Treatment Outcome
D017312:Toremifene; D017239:Paclitaxel